Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases

• Published in: Journal of the neurological sciences Vol. 264; no. 1; pp. 18 - 21
• Main Authors: Liu, Chin-San, Cheng, Wen-Ling, Kuo, Shou-Jen, Li, Jie-Yuan, Soong, Bing-Wen, Wei, Yau-Huei
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.01.2008; Elsevier Science
• Subjects: Adult; Base Sequence - genetics; Biological and medical sciences; CAG repeat numbers; Copy number; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; DNA, Mitochondrial - analysis; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Down-Regulation - genetics; Female; Gene Dosage - genetics; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Heredodegenerative Disorders, Nervous System - blood; Heredodegenerative Disorders, Nervous System - diagnosis; Heredodegenerative Disorders, Nervous System - genetics; Humans; Huntington Disease - blood; Huntington Disease - diagnosis; Huntington Disease - genetics; Leukocyte; Leukocytes - metabolism; Male; Medical sciences; Middle Aged; Mitochondrial DNA; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Muscular Atrophy, Spinal - blood; Muscular Atrophy, Spinal - diagnosis; Muscular Atrophy, Spinal - genetics; Mutation - genetics; Neurodegenerative disorders; Neurology; Oxidative Stress - genetics; Peptides - genetics; Polyglutamine; Predictive Value of Tests; Spinocerebellar Ataxias - blood; Spinocerebellar Ataxias - diagnosis; Spinocerebellar Ataxias - genetics; Trinucleotide Repeat Expansion - genetics; Mitochondrial DNA; Polyglutamine; CAG repeat numbers; Copy number; Leukocyte; Neurodegenerative disorders; Human; Nervous system diseases; Depletion
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2007.07.016

Polyglutamine (poly-Q) diseases are late-onset neurodegenerative disorders arising from the expansion of an unstable CAG repeat in the affected gene, which is translated to a tract of glutamine residues. This kind of mutant proteins may be aggregated and accumulated, and thereby enhance cellular oxidative stress. In one of our previous studies ( Free Radic. Res. 2003;37:1307-17), we found that alteration in the leukocyte mtDNA content is very sensitive to the level of oxidative stress in blood. Thus, we proposed that leukocyte mtDNA content may be used as a biomarker to predict the severity of clinical manifestation of poly-Q diseases. We recruited 50 healthy subjects and 114 patients with poly-Q diseases, including spinal cerebellar atrophy 2/3, spinal bulbar muscular atrophy, and Huntington chorea. We found that mtDNA in leukocytes was depleted in patients with poly-Q diseases ( P < 0.05). Moreover, the results showed that patients with lower mtDNA content more frequently manifested multiple-symptom disorders and had high CAG repeat numbers in the mutant genes. In conclusion, we suggest that leukocyte mtDNA content correlates with the length of GAG repeat and may serve as an index of the severity of poly-Q diseases.